The proposed Forsyth Caries Center will integrate a clinical core effect entailing an 18 month root caries incidence study (n=400) with microbial, physico-chemical, and dietary investigations collectively aimed at implicating a segment of the microfluora (the 'low pH' non-mutans streptococci or "low pH' non-MS) in the process of ongoing disease activity, while relating said organisms (as well as mutans streptococci and some other selected indicated organisms) to a battery of plaque parameters (putative, pathognomonic, plaque characteristics or PPPC) and diet. The large scale microbial assay work be will be made possible by the development and application of DNA probes. The microbiological studies will yield a comprehensive picture of the plaque flora with respect to two major caries--relevant bacterial traits viz., capability for acidogenesis at acid plaque pH and acid tolerance. In addition to the PPPC studies above, the physico-chemical effort will include in vitro investigations to assess the relative influence upon dentin and enamel demineralization of (i) salivary pellicle formation (ii) the adsorption of relevant salivary proteins. (iii) inherent differences in ultra- structure and mineral properties, (iv) degree of saturation in experimental solutions and (v) fluoride ion concentration, so as to provide a unified picture of the caries process. The highly productive in vitro salivary chemistry studies of the past have shown that specific proteins bacterial adhesion. It is important now to test this hypothesis in vivo. Protein coated enamel blocks will be placed in the mouth and the initial adhesion of selected bacteria will be determined. Additional studies will test the hypothesis that a subject's salivary protein profile determines pellicle composition which, it turn, determines selective bacterial adhesion. The in vivo studies will be complemented by a continuing laboratory effort aimed at testing the hypothesis that some salivary and serum proteins and bacterial macromolecules act as inhibitors of adhesion of specific oral bacterial to HA-absorbed salivary proteins. The proposed five year Center effort has the potential for implicating a new group of organisms in the caries process and characterizing their relationship to PPPC and diet while producing the most explanatory models of the caries process to date. In addition, the identity and pathogenic features of the target organisms will be fully elaborated and a comprehensive collection of DNA probes for potential cariogenic bacteria will be developed. The salivary studies will strongly complement the program by initiating the first major in vivo effort to relate specific bacterial adhesion to pellicle composition while advancing the studies of adhesion dynamics in the laboratory.